The long-term goal of this research is to elucidate the apparently intertwined molecular bases of plant susceptibility to plant pathogens and plant basal immunity to human pathogens. In nature, plants are immune to most microbes, including the majority of human pathogens;however, plants are extremely susceptible to a subset of phytopathogenic bacteria that have evolved specific virulence strategies. One of the most important bacterial virulence strategies is the type III secretion system, which injects a diverse array of effector proteins into the host cell to promote pathogenesis. Little is known about the molecular mechanisms by which these effector proteins modulate plant cellular functions. Recent studies have given exciting clues: some effector proteins are involved in suppressing various forms of plant immunity. In particular, two Pseudomonas syringae effectors, AvrPto and HopPtoM, suppress basal innate immunity in Arabidopsis. Preliminary results show that AvrPto may target a polarized extracellular trafficking pathway mediated by the RabE family of G proteins. HopPtoM promotes the disappearance of several host proteins (AtMINs). To elucidate the molecular mechanisms by which AvrPto and HopPtoM suppress basal immunity in Arabidopsis, we will (1) characterize the RabE-mediated vesicle trafficking pathway in Arabidopsis immunity, (2) determine the mechanism by which AvrPto inhibits RabE function, (3) characterize the virulence activity of HopPtoM, and (4) determine the role of AtMIN proteins in HopPtoM-specific virulence. An integrated approach using molecular genetic, cell biological, transgenic, and pathological methods will be taken to accomplish these aims. The proposed research will not only contribute to the fundamental knowledge of how bacterial pathogens cause disease in higher eukaryotes, but also increase our understanding of the virtually unexplored molecular basis of plant immunity to human pathogens. Food poisoning caused by human pathogen contamination is a major public health concern.